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  • potent
  • PGE2>Prostaglandin F2alpha>PGI2=thromboxane A2, with PGD2 being more than 100-fold more potent than PGE2 in binding to and stimulating DP1. (wikipedia.org)
  • L-644,698, BW 245C, BW A868C, and ZK 110841, have been synthesized, found to be about as potent as PGD2 in binding to and stimulating DP1, and used to study the function of this receptor. (wikipedia.org)
  • Antagonists
  • While several A2A receptor antagonists have progressed to clinical trials for the treatment of Parkinson's disease, A2AR blockade in the context of cancer is less characterized. (wikipedia.org)
  • Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants. (wikipedia.org)
  • Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates. (wikipedia.org)
  • Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). (wikipedia.org)
  • DP1 gene knockout and/or DP1 inhibition by receptor antagonists markedly reduces airway inflammation, obstruction, hypersensitivity, and pro-allergic cytokine and chemokine production in a mouse model of ovalbumin-induced asthma as well as allergic symptoms in a guinea pig model of allergic conjunctivitis, rhinitis, and asthma. (wikipedia.org)
  • NECA
  • A series of new 2-alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N-ethyluronamid(NECA) and of N-ethyl-l'-deoxy-l'-(6-amino-2-hexynyl-9H-purin-9-yl)-b-D-ribofuranuronamid(1e, HENECA), bearing hydroxy, amino, chloro, and cyano groups in the side chain, were synthesized. (unicam.it)
  • The presence of an a-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to compounds endowed with sub-nanomolar affinity in binding studies. (unicam.it)
  • To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
  • Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (physiology.org)
  • Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (physiology.org)
  • tyrosine kinase re
  • ATP is crucial for ALOX5's metabolic activity A proline-rich region (residues 566-577), sometimes termed a SH3-binding domain, which promotes its binding to proteins with SH3 domains such as Grb2 and may thereby link the enzyme's regulation to tyrosine kinase receptors. (wikipedia.org)
  • myocardial
  • Adenoscan® (adenosine) is an approved pharmacological stress agent indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately. (clinicaltrials.gov)
  • Objectives In the absence of effective clinical pharmacotherapy for prevention of reperfusion-mediated injury, this study re-evaluated the effects of intracoronary adenosine on infarct size and no-reflow in a porcine model of acute myocardial infarction using clinical bolus and experimental high-dose infusion regimens. (onlinejacc.org)
  • Conclusions During reperfusion, intracoronary adenosine can limit infarct size and no-reflow in a porcine model of acute myocardial infarction. (onlinejacc.org)
  • As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
  • The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. (wikipedia.org)
  • Adenosine is used as an adjunct to thallous (thallium) chloride TI 201 or Tc99m myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. (wikipedia.org)
  • inhibits
  • This kinase inhibits Gαq-phospholipase C-inositol 1,4,5-triphosphate signaling and the mobilization of calcium inside the cell for thromboxane A2. (wikipedia.org)
  • Acute ethanol exposure, a brief period of ethanol use, inhibits Ca2+ flow through NMDA receptors in the hippocampus, the brain structure particularly important in memory formation. (wikipedia.org)
  • mGluR
  • In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. (aspetjournals.org)
  • anti-inflammatory
  • Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. (pubmedcentralcanada.ca)
  • physiological
  • A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. (aspetjournals.org)
  • However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. (wikipedia.org)
  • As these "classical" opioid receptors were identified 30 years earlier in the mid-1960s, the physiological and pharmacological characterization of NOP as well as therapeutic development targeting this receptor remain decades behind. (wikipedia.org)
  • vascular
  • The A2b adenosine receptor (A2bAR) is highly abundant in bone marrow macrophages and vascular smooth muscle cells (VSMC). (pnas.org)
  • To examine the functional significance of this receptor expression, we applied a femoral artery injury model to A2bAR knockout (KO) mice and showed that the A2bAR prevents vascular lesion formation in an injury model that resembles human restenosis after angioplasty. (pnas.org)
  • In the current study we examined the role of vascular and bone marrow adenosine receptors in vascular response to injury using a model that mimics human restenosis after angioplasty. (pnas.org)
  • A1 receptors are also present in smooth muscle throughout the vascular system. (wikipedia.org)
  • Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. (wikipedia.org)
  • inflammation
  • In general, the A2-type receptors have been described as sensors of tissue damage during an immune response ( 2 ), and A2aARs have been described as having a nonredundant role in the attenuation of inflammation and tissue damage in vivo ( 3 ). (pnas.org)
  • These findings suggest that during pathological conditions such as inflammation or trauma, the significant amounts of cellular adenosine which are released may increase the production of NO by macrophage. (nus.edu.sg)
  • regulation
  • This study demonstrates that nucleotide receptors in this model of renal epithelium initiate distinct regulation of Na-K-Cl cotransport. (rti.org)
  • The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease. (wikipedia.org)
  • Adenosine also plays a role in regulation of blood flow to various organs through vasodilation. (wikipedia.org)
  • This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. (wikipedia.org)
  • compounds
  • The compounds were studied in binding and functional assays to assess their potency for the A2 compared to A1 adenosine receptor. (unicam.it)
  • Although NOP shares high sequence identity (~60%) with the 'classical' opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), it possesses little or no affinity for opioid peptides or morphine-like compounds. (wikipedia.org)
  • hypoxia
  • Because adenosine production increases in hypoxia, the issue of a role of the nucleoside in the renal injury following ischemia reperfusion has been studied extensively. (springer.com)
  • protects
  • Experimental evidence supports the notion that adenosine protects against ischemia-induced acute kidney injury by directly acting on renal endothelial and tubular A 1 AR. (springer.com)
  • induces
  • Additional studies suggest that adenosine induces apoptosis of human arterial smooth muscle cells, which is mediated via the A2bAR in a cAMP-dependent pathway ( 7 ). (pnas.org)
  • platelets
  • When it is added to saline-diluted whole blood in the test cuvette, it stimulates the ADP receptors on platelets, activating the platelets. (wikipedia.org)
  • Binding of TRAP-6 to PAR-1 causes a conformational change in the GPIIb/IIIa receptors on platelets, giving them high affinity for fibrinogen. (wikipedia.org)
  • renal
  • The dominant effect of an elevation of plasma adenosine in the renal vasculature is an A 2A AR- and A 2B AR-mediated vasodilatation that increases global as well as medullary renal blood flow and is in part endothelium-dependent. (springer.com)
  • Baranowski RL, Westenfelder C (1994) Estimation of renal interstitial adenosine and purine metabolites by microdialysis. (springer.com)
  • Beach RE, Watts BA 3rd, Good DW et al (1991) Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions. (springer.com)
  • membrane
  • It is the case for the vast majority of responses as a consequence of the binding of the primary messengers to membrane receptors. (wikipedia.org)
  • reperfusion
  • In protocol A, an intracoronary bolus of 3 mg adenosine injected over 1 min (n = 5) or saline (n = 10) was administered at reperfusion. (onlinejacc.org)
  • In protocol B, an intracoronary infusion of 50 μg/kg/min adenosine (n = 15) or saline (n = 21) was administered starting 5 min prior to reperfusion and continued throughout the 2-h reperfusion period. (onlinejacc.org)
  • These findings warrant reconsideration of adenosine as an adjuvant therapy during early reperfusion. (onlinejacc.org)
  • GPCRs
  • A GPCR oligomer is a protein complex that consists of a small number (ὀλίγοι oligoi "a few", μέρος méros "part, piece, component") of G protein-coupled receptors (GPCRs). (wikipedia.org)
  • Receptor homodimers - which consist of two identical GPCRs - are the simplest homomeric GPCR oligomers. (wikipedia.org)
  • Receptor heterodimers - which consist of two different GPCRs - are the simplest heteromeric GPCR oligomers. (wikipedia.org)
  • The first direct evidence that GPCRs functioned as oligomers in vivo came from Overton and Blumer in 2000 by fluorescence resonance energy transfer (FRET) analysis of the α-factor receptor in the yeast Saccharomyces cerevisiae. (wikipedia.org)
  • affinity
  • However, these analogues also possess good A1 receptor affinity resulting in low A2 selectivity. (unicam.it)
  • The presence of an a-quaternary carbon such as the 3-hydroxy-3,5-dimethyl-1-hexynyl (12) and the 3-hydroxy-3-phenyl-1-butynyl(1 5) derivatives markedly reduced the antiaggregatory potency without affecting the A2 affinity. (unicam.it)
  • pathways
  • NOP acting through Gαi/o pathways has also been shown to activate Phospholipase A2 (PLA2), thereby initiating Mitogen-activated protein kinase (MAPK) signaling cascades. (wikipedia.org)
  • inhibition
  • After the secretion, 5-HT increases the effects of prothrombotic agents by its binding with 5-HT2 receptors Thromboregulation is also in charge of regulating the process of clot elimination, called primary hemostasis inhibition. (wikipedia.org)
  • Inhibition of COX1, as with acetylsalicylic acid, and inhibition or absence of GPIIb/IIIa receptor, as seen in Glanzmann's thrombasthenia, will reduce platelet aggregation in response to arachidonic acid. (wikipedia.org)
  • neurotransmitter
  • Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. (wikipedia.org)
  • A released neurotransmitter is typically available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. (wikipedia.org)
  • Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission. (wikipedia.org)
  • Drugs
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (nih.gov)
  • The existence of receptor oligomers is a general phenomenon, whose discovery has superseded the prevailing paradigmatic concept of the function of receptors as plain monomers, and has far-reaching implications for the understanding of neurobiological diseases as well as for the development of drugs. (wikipedia.org)
  • The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. (wikipedia.org)
  • Antiplatelet drugs like clopidogrel and prasugrel irreversibly inhibit the ADP receptor P2Y12, leading to a decreased ADP-induced platelet aggregation. (wikipedia.org)
  • Drugs that inhibit the GPIIb/IIIa receptor, e.g. eptifibatide, can also reduce or eliminate the ADP-induced platelet response. (wikipedia.org)
  • mice
  • ASP5854 ameliorated A(2A) agonist 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680)- and haloperidol-induced catalepsy in mice, with the minimum effective doses of 0.32 and 0.1 mg/kg, respectively, and it also improved haloperidol-induced catalepsy in rats at doses higher than 0.1 mg/kg. (curehunter.com)
  • Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
  • activity
  • The hydrophobicity index (k') of the new nucleosides barely correlated with the binding data, whereas high k' values were associated with increased A2 vs A1 selectivity but with reduced activity in all unctional assays. (unicam.it)
  • Nitrite production and NOS activity in the RAW 264.7 cells were increased up to 2.5 fold after co-exposure of the cells to LPS and adenosine or its agonists, as compared to LPS alone. (nus.edu.sg)
  • Adenosine and its agonists had no effect on NOS activity when incubated alone with RAW 264.7 cells. (nus.edu.sg)
  • The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. (wikipedia.org)
  • This receptors may have intrinsic catalytic activity or may be coupled to effector enzymes, or may also be associated to ionic channels. (wikipedia.org)
  • CamK Rapid changes in Ca2+ concentration, influenced by receptors such as those described above, regulate the activity of CaMKs. (wikipedia.org)